Analysis of Corticosteroids in Immune Checkpoint Inhibitor(ICE)Induced Myocarditis-A Systematic Review of 352 Screened Articles

Introduction:Immune Checkpoint Inhibitors(ICI)is used as a single agent or as a combination therapies for early or late-stage malignancies.The common malignancies that ICI targets include the following:melanoma, lung cancer, renal cell carcinoma, and hematological malignancies such as Hodgkin lymphoma.ICI use is associated with many immune-related adverse events, and ICI-induced myocarditis is one of the rare and most severe AE with a high mortality rate. There is no consensus evidence-based treatment guideline; the expert recommendation is to use high-dose steroids. We aim in this review to assess the effectiveness of steroids in treating ICI-induced myocarditis. Methods: We searched the following database Pubmed, Scopus, Cinhale, and Google Scholar, using the following keywords: ICI-induced myocarditis, treatment, steroid. We included articles in the English language, case reports, case series, and published in the last five years. Results: 352 articles were screened using PRISMA guidelines. After excluding the articles that were duplicate, irrelevant, and did not meet inclusion criteria, 35 articles with a total number of 50 patients were included. All patients treated with ICI either as a single or combination regimen. The onset of symptoms post-initiation varied from one day to a year. 46 out of the 50 cases received high doses of Intravenous steroids as a loading dose followed by an oral or intravenous maintenance dose. Out of 50 patients 14 patients (28 %) died but 34 (68 %) patients survived, and 2 (4 %) patients data were not available. The mean age of the patients was 66.31+/-14.071 (range 23-88 years), 29 were male (58%), 21 were female (42%). Most of the cases were from the USA (42%), followed by Australia (20 %), Japan (14%), Germany, France, and China (4%), Switzerland, Canada, and Spain (2%), and for (6%) cases. A total of 23 patients had cardiovascular comorbidities (46%), which were HTN (14 patients, 60.87%), hyperlipidemia (5 patients, 21.73%), and less than 1 % of patients had myocardial ischemia, congestive heart failure, atrial fibrillation, and peripheral vascular disease. While 26 patients (52%) had normal basal cardiac status. Conclusion: Our results showed that high doses of steroids were effective in controlling cardiac myocyte inflammation and mortality by 28%. The race was not included in the analysis as it was not reported. More in depth studies are needed to provide a broader representation of steroids in myocarditis.

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POSSIBILITIES OF PROTON THERAPY IN THE TREATMENT OF PEDIATRIC SKULL BASE CHORDOMAS: A CASE SERIES REPORT

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2021-100-3-272-279 ◽

2021 ◽

Vol 100 (3) ◽

pp. 272-279

Author(s):

N.A. Vorobyov ◽

◽

N.I. Martynova ◽

D.A. Antipin ◽

K.F. Boiko ◽

...

Keyword(s):

Proton Therapy ◽

Malignant Tumors ◽

Case Reports ◽

Case Series ◽

Photon Radiation ◽

High Dose ◽

Primary Bone Tumors ◽

Case Series Report ◽

High Doses ◽

Skull Base Chordomas

Chordomas are rare malignant tumors that account for no more than 4% of primary bone tumors. The incidence of chordomas in children does not exceed 5%. Tumor removal is the primary method of treatment, however, due to the high frequency of non-radical surgery, most patients require an adjuvant course of radiotherapy. Photon radiation therapy in doses of 50–60 Gy does not provide the required antitumor effect. At the same time, the use of a proton beam allows delivering a dose of 72 Gy or more with low toxicity. The article presents 4 clinical case reports of base-skull chordoma in children describing their own experience with proton therapy. An analysis of radiation exposure plans was carried out, with an evaluation of the main qualitative indicators characterizing the high-dose coverage of tumours and the radiation load on healthy tissues. The case reports described confirm that the technique of proton irradiation with a pencil beam makes it possible to safely administer ultra-high doses of radiation in close proximity to healthy tissues, including in children. Further improvement of the irradiation planning technique is required, which will improve the target coverage with a high dose of ionizing radiation.

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Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

East Africa Science ◽

10.24248/easci.v1i1.4 ◽

2019 ◽

Vol 1 (1) ◽

pp. 49-56

Author(s):

Mariam M. Mirambo ◽

Lucas Matemba ◽

Mtebe Majigo ◽

Stephen E. Mshana

Keyword(s):

Virus Infection ◽

Neural Tube ◽

Zika Virus ◽

English Language ◽

Case Reports ◽

Case Series ◽

Epidemiological Studies ◽

Ocular Manifestations ◽

Zika Virus Infection ◽

N 93

Background: Zika virus infection during pregnancy has been recently associated with congenital microcephaly and other severe neural tube defects. However, the magnitude of confirmed cases and the scope of these anomalies have not been extensively documented. This review focuses on the magnitude of laboratory-confirmed congenital Zika virus cases among probable cases and describing the patterns of congenital anomalies allegedly caused by the Zika virus, information which will inform further research in this area. Methods: We conducted a literature search for English-language articles about congenital Zika virus infection using online electronic databases (PubMed/MEDLINE, POPLINE, Embase, Google Scholar, and Web of Knowledge). The search terms used were, “zika”, “pregnancy”, [year], “microcephaly”, “infants”, “children”, “neonates”, “foetuses”, “neural tube defect”, and “CNS manifestations” in different combinations. All articles reporting cases or case series between January 2015 and December 2016 were included. Data were entered into a Microsoft Excel database and analysed to obtain proportions of the confirmed cases and patterns of anomalies. Results: A total of 24 articles (11 case series, 9 case reports, and 4 others) were found to be eligible and included in this review. These articles reported 919 cases, with or without microcephaly, presumed to have congenital Zika virus infection. Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 (27.6%; 95% confidence interval, 24.5% to 30.8%) were confirmed to be Zika virus-positive. In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurological defects.

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Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

East Africa Science ◽

10.24248/easci.v1.iss1.4 ◽

2019 ◽

Vol 1 (1) ◽

pp. 49-56

Author(s):

Mariam M. Mirambo ◽

Lucas Matemba ◽

Mtebe Majigo ◽

Stephen E. Mshana

Keyword(s):

Virus Infection ◽

Neural Tube ◽

Zika Virus ◽

English Language ◽

Case Reports ◽

Case Series ◽

Epidemiological Studies ◽

Ocular Manifestations ◽

Zika Virus Infection ◽

N 93

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Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835921992989 ◽

2021 ◽

Vol 13 ◽

pp. 175883592199298

Author(s):

Orthi Shahzad ◽

Nicola Thompson ◽

Gerry Clare ◽

Sarah Welsh ◽

Erika Damato ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Case Reports ◽

Case Series ◽

Simple Algorithm ◽

Cancer Therapeutics ◽

Management Algorithm ◽

Ocular Symptoms ◽

Systemic Corticosteroids ◽

Permanent Loss

Ocular immune-related adverse events (IrAEs) associated with use of checkpoint inhibitors (CPIs) in cancer therapeutics are relatively rare, occurring in approximately 1% of treated patients. Recognition and early intervention are essential because the degree of tissue damage may be disproportionate to the symptoms, and lack of appropriate treatment risks permanent loss of vision. International guidelines on managing ocular IrAEs provide limited advice only. Importantly, local interventions can be effective and may avoid the need for systemic corticosteroids, thereby permitting the continuation of CPIs. We present a single institution case series of eight affected patients managed by our multidisciplinary team. Consistent with previously published series and case reports, we identified anterior uveitis as the most common ocular IrAE associated with CPIs requiring intervention. Based on our experience, as well as published guidance, we generated a simple algorithm to assist clinicians efficiently manage patients developing ocular symptoms during treatment with CPIs. In addition, we make recommendations for optimising treatment of uveitis and address implications for ongoing CPI therapy.

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Drug-Induced Restless Legs Syndrome

Annals of Pharmacotherapy ◽

10.1177/1060028018760296 ◽

2018 ◽

Vol 52 (7) ◽

pp. 662-672 ◽

Cited By ~ 9

Author(s):

Edna Patatanian ◽

Melanie K. Claborn

Keyword(s):

Restless Legs Syndrome ◽

English Language ◽

Case Reports ◽

Data Extraction ◽

Case Series ◽

Predisposing Factors ◽

Drug Induced ◽

Restless Legs ◽

Drug Classes ◽

Study Selection

Objective: To review the literature on drug-induced restless legs syndrome (DI-RLS). Data Sources: The review included a search for English-language literature from 1966 to December 2017 in the MEDLINE, PubMed, and Ovid databases using the following search terms: restless legs syndrome (RLS), periodic limb movement, adverse effects, and drug-induced. In addition, background articles on the pathophysiology, etiology, and epidemiology of RLS were retrieved. Bibliographies of relevant articles were reviewed for additional citations. Study Selection and Data Extraction: All case reports, case series, and review articles of DI-RLS were identified and analyzed. There were only a small number of controlled clinical trials, and most data were from case reports and case series. Results: Several drugs and drug classes have been implicated in DI-RLS, with antidepressants, antipsychotics, and antiepileptics having the most evidence. In addition, RLS may be linked with a number of disorders or underlying predisposing factors as well. Conclusions: The prevalence of RLS is variable and ranges from 3% to 19% in the general population. There are many predisposing factors to RLS, but an emerging body of evidence suggests that there is an association between numerous drugs and RLS.

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Bacillus cereus Typhlitis in a Patient with Acute Myelogenous Leukemia: A Case Report and Review of the Literature

Case Reports in Infectious Diseases ◽

10.1155/2018/7510715 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4

Author(s):

James D. Denham ◽

Sowmya Nanjappa ◽

John N. Greene

Keyword(s):

Bacillus Cereus ◽

Acute Myelogenous Leukemia ◽

English Language ◽

Neutropenic Patient ◽

Hematologic Malignancy ◽

Case Reports ◽

Clinical Manifestations ◽

Case Series ◽

Myelogenous Leukemia ◽

Acute Myelogenous

Bacillus cereus is a Gram-positive rod that is now recognized as a rare cause of frank disease in the neutropenic hematologic malignancy patient. Because this pathogen is rarely isolated in clinical specimens, no large studies exist to guide the management of these acutely ill patients. Individual case reports and case series exist in the literature describing various clinical manifestations of B. cereus in the neutropenic patient including bacteremia/septicemia, pneumonia, meningitis/encephalitis, hepatic abscesses, and gastritis. In this report, we describe a case of typhlitis caused by B. cereus in a 74-year-old female with recently diagnosed acute myelogenous leukemia (AML), and we summarize the available English language literature to draw tentative conclusions regarding the clinical manifestations of this organism.

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Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-211560 ◽

2017 ◽

Vol 76 (12) ◽

pp. 2061-2064 ◽

Cited By ~ 73

Author(s):

Sang Taek Kim ◽

Jean Tayar ◽

Van Anh Trinh ◽

Maria Suarez-Almazor ◽

Salvador Garcia ◽

...

Keyword(s):

Checkpoint Inhibitors ◽

Case Reports ◽

Unmet Need ◽

Case Series ◽

Receptor Antibody ◽

Improved Outcomes ◽

Clinical Scenarios ◽

Significant Clinical Improvement ◽

Tnfα Inhibitor ◽

Factor Α

BackgroundImmune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with numerous cancers. However, these therapies are associated with immune-related adverse events (irAEs), which are inflammatory side effects potentially affecting any organ. Cases of ICI-induced inflammatory arthritis have also been reported. In general, mild irAEs are treated with corticosteroids, while tumour necrosis factor-α (TNFα) inhibitors are reserved for refractory cases. However, prolonged use of TNFα inhibitor (TNFαi) can induce widespread, significant immunosuppression, which can negatively impact the antitumour efficacy of ICI therapy. Therefore, in clinical scenarios where patients develop severe immunotherapy-induced irAEs, an unmet need exists for alternative therapeutic strategies that are effective and without immune dampening effects.Case reportsThe anti-interleukin (IL)−6 receptor antibody, tocilizumab, is a biological agent Food and Drug Administration approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Here, we report on three patients who developed severe polyarthritis while receiving ICI therapy and were treated with tocilizumab. All three patients demonstrated significant clinical improvement; one patient maintained a durable antitumour response derived from checkpoint inhibition.ConclusionsThese three cases suggest that anti-IL-6 receptor antibody may be an effective alternative to corticosteroids or TNFαi for the treatment of arthritis irAEs.

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A Review and Assessment of Drug-Induced Thrombocytosis

Annals of Pharmacotherapy ◽

10.1177/1060028018819450 ◽

2018 ◽

Vol 53 (5) ◽

pp. 523-536 ◽

Cited By ~ 4

Author(s):

Quyen T. Vo ◽

Dennis F. Thompson

Keyword(s):

English Language ◽

Web Of Science ◽

Case Reports ◽

Data Extraction ◽

Case Series ◽

Search Term ◽

Drug Induced ◽

Reactive Thrombocytosis ◽

All Trans Retinoic Acid ◽

Mesh Terms

Objectives: The purpose of this article is to review the current literature on drug-induced thrombocytosis with the goal of critically assessing causality and providing a comprehensive review of the topic. Thrombopoietic growth factors, such as thrombopoietin-receptor agonists (romiplostim and eltrombopag) and erythropoietin are not included in our review. Data Sources: The literature search included published articles limited to the English language and humans in MEDLINE, EMBASE, and Web of Science databases. MEDLINE/PubMed (1966 to September 2018) was searched using the MeSH terms thrombocytosis/chemically-induced and thrombocytosis/etiology. EMBASE (1980 to September 2018) was searched using the EMTAGS thrombocytosis/side effect. Web of Science (1970 to September 2018) was searched using the search term thrombocytosis. References of all relevant articles were reviewed for additional citations and information. Study Selection and Data Extraction: Review articles, clinical trials, background data, case series, and case reports of drug-induced thrombocytosis were collected, and case reports were assessed for causality using a modified Naranjo nomogram. Data Synthesis: Drug-induced thrombocytosis, a form of reactive thrombocytosis cannot be easily differentiated from more common etiologies of reactive thrombocytosis. In all, 43 case reports of drug-induced thrombocytosis from a wide variety of drugs and drug classes were reviewed using a modified Naranjo probability scale that included criteria specific for thrombocytosis. Conclusions: Drug-induced thrombocytosis is a relatively rare adverse drug reaction. The strongest evidence of causality supports low-molecular-weight heparins and neonatal drug withdrawal. Weaker evidence exists for all-trans retinoic acid, antibiotics, clozapine, epinephrine, gemcitabine, and vinca alkaloids.

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Oral White Lesions: An Updated Clinical Diagnostic Decision Tree

Dentistry Journal ◽

10.3390/dj7010015 ◽

2019 ◽

Vol 7 (1) ◽

pp. 15 ◽

Cited By ~ 9

Author(s):

Hamed Mortazavi ◽

Yaser Safi ◽

Maryam Baharvand ◽

Soudeh Jafari ◽

Fahimeh Anbari ◽

...

Keyword(s):

Decision Tree ◽

English Language ◽

Case Reports ◽

Case Series ◽

Oral Diseases ◽

Diagnostic Decision ◽

General Search ◽

Retrospective Cohort Studies ◽

Special Pattern ◽

Meta Analyses

Diagnosis of oral white lesions might be quite challenging. This review article aimed to introduce a decision tree for oral white lesions according to their clinical features. General search engines and specialized databases including PubMed, PubMed Central, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used to find relevant topics by means of MeSH keywords such as “mouth disease”, “oral keratosis”, “oral leukokeratosis”, and “oral leukoplakia”. Related English-language articles published since 2000 to 2017, including reviews, meta-analyses, and original papers (randomized or nonrandomized clinical trials; prospective or retrospective cohort studies), case reports, and case series about oral diseases were appraised. Upon compilation of data, oral white lesions were categorized into two major groups according to their nature of development: Congenital or acquired lesions and four subgroups: Lesions which can be scraped off or not and lesions with the special pattern or not. In total, more than 20 entities were organized in the form of a decision tree in order to help clinicians establish a logical diagnosis by a stepwise progression method.

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Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001009 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001009

Author(s):

Sara Bedrose ◽

Kevin Charles Miller ◽

Lina Altameemi ◽

Mohamed S Ali ◽

Sameh Nassar ◽

...

Keyword(s):

Systemic Therapy ◽

Salvage Therapy ◽

Checkpoint Inhibitors ◽

Single Agent ◽

Case Series ◽

Progression Free Survival ◽

Adrenal Cortical Carcinoma ◽

Retrospective Case ◽

First Case ◽

Platinum Based Chemotherapy

BackgroundThere is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.MethodsA retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC.ResultsEight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21–49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2–9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8–not reached) and median duration of therapy was 8.5 months (range 2–22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events.ConclusionsIn our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response.

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